Requirement of a reactive aldehyde moiety for aldehyde-mediated protection against cis-dichlorodiammineplatinum-induced cell inactivation.
The effect of the aromatic aldehydes benzaldehyde and salicylaldehyde, the glucose-acetal derivative 4,6-benzylidene-D-glucose (BG) and the glucoside salicylaldehyde-beta-D-glucoside (helicin) on cell inactivation induced by cis-dichlorodiammineplatinum (cis-DDP) was investigated using cultured human NHIK 3025 cells. Cell inactivation was measured as loss in the ability of single cells to give rise to macroscopic colonies following drug treatment. The fraction of cells surviving a 2 hr treatment with 10 microM cis-DDP increased from 0.012 +/- 0.004 to 0.10 +/- 0.03 when treatment was combined with at least 1 mM benzaldehyde or at least 0.2 mM salicylaldehyde. Of the two sugar-aldehyde derivatives only helicin protected cells from the inactivating effect of cis-DDP, although to a much lesser extent than either benzaldehyde or salicylaldehyde. While helicin retains the aldehyde moiety of salicylaldehyde, BG does not possess any free aldehyde group. Using synchronized cells we found these effects to appear in all phases of the cell cycle. Measurements of cell-associated platinum indicated that the degree of protection from the inactivating effects of cis-DDP by these aldehydes was related to the degree of reduced platinum accumulation. We conclude that this reduced accumulation may represent an inhibition of specific cell membrane uptake sites via Schiff based formation between membrane amino groups and aldehydes.
Dornish
J M
JM
Department of Tissue Culture, Norwegian Radium Hospital, Oslo.
Pettersen
E O
EO
D000447:Aldehydes / Q000378:metabolism / Q000494:pharmacology*; D001547:Benzaldehydes / Q000378:metabolism / Q000494:pharmacology*; D002453:Cell Cycle; D002470:Cell Survival / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D004336:Drug Antagonism; D006801:Humans; D010984:Platinum / Q000032:analysis; D012545:Schiff Bases / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000447:Aldehydes; D001547:Benzaldehydes; D012545:Schiff Bases; C013243:salicylaldehyde; D010984:Platinum; D002945:Cisplatin